Pharmaceutical compositions
Inventors
Brisander, Magnus • Demirbüker, Mustafa • Jesson, Gérald • Malmsten, Martin • Dérand, Helene
Assignees
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Publication Number
US-12144804-B1
Publication Date
2024-11-19
Expiration Date
Abstract
The present invention relates to the field of methods for providing pharmaceutical compositions comprising poorly water-soluble drugs. In particular the present invention relates to compositions comprising stable, amorphous hybrid nanoparticles, comprising at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix-forming component, useful in pharmaceutical compositions and in therapy.
Core Innovation
The invention relates to a tablet comprising particles having amorphous dasatinib and methacrylic acid and ethylacrylate copolymer, copolyvidone, or a combination thereof. The particles exclude a pharmaceutically acceptable solubilizer, and the tablet further comprises one or more excipients. The described particle system is directed to maintaining amorphous dasatinib within the tablet formulation.
The disclosure further concerns stable, essentially amorphous hybrid nanoparticles made from poorly water-soluble protein kinase inhibitors, including tyrosine kinase inhibitors, together with polymeric stabilizing and matrix-forming components. The particles have high amorphous content and stability over an extended period of time, and the polymeric stabilizing and matrix-forming components include methacrylic acid and ethylacrylate copolymer, copolyvidone, or combinations thereof.
The document additionally reports dissolution and exposure performance for stable, amorphous hybrid nanoparticles containing poorly soluble anticancer kinase inhibitors. Dissolution and solubilization are described in intestinal and gastric biorelevant media, including FaSSIF and FeSSIF, with comparisons versus raw crystalline drug, and the compositions are related to reduced food-effect indications and reported plasma exposure examples for selected PKIs.
Claims Coverage
The independent claim set centers on a tablet formulation with amorphous dasatinib in particles containing methacrylic acid and ethylacrylate copolymer and/or copolyvidone, while the particles exclude a pharmaceutically acceptable solubilizer and the tablet contains one or more excipients. The document also includes a method for treating leukemia by administering the tablet.
Tablet with amorphous dasatinib particles
A tablet comprising particles including amorphous dasatinib.
Particles with methacrylic acid and ethylacrylate copolymer or copolyvidone
The particles include methacrylic acid and ethylacrylate copolymer, copolyvidone, or a combination thereof.
Excluding pharmaceutically acceptable solubilizer from particles
The particles exclude a pharmaceutically acceptable solubilizer.
Tablet includes one or more excipients
The tablet comprises one or more excipients.
Leukemia treatment by administering the tablet
A method for treating leukemia by administering to a patient in need thereof a therapeutically effective amount of the tablet.
Leukemia indication for lymphocytic and/or myelogenous leukemia
The method wherein the leukemia is at least one selected from lymphocytic leukemia and myelogenous leukemia.
Overall, the claim coverage centers on a tablet formulation with amorphous dasatinib in particles containing methacrylic acid and ethylacrylate copolymer and/or copolyvidone, while the particles exclude a pharmaceutically acceptable solubilizer and the tablet contains one or more excipients. The coverage further includes administering a therapeutically effective amount of that tablet for treating leukemia, including lymphocytic leukemia and/or myelogenous leukemia.
Stated Advantages
Improved dissolution and solubilization performance versus raw crystalline drug, including increased initial dissolution rate and apparent solubility metrics.
Reduced food-effect indications via performance in biorelevant media.
In vivo performance is supported by reported plasma exposure examples for selected PKIs.
Documented Applications
Use for treating leukemia by administering a therapeutically effective amount of the tablet.
Leukemia treatment specifically for lymphocytic leukemia and/or myelogenous leukemia.
Dissolution and exposure performance for stable, amorphous hybrid nanoparticles containing poorly soluble anticancer kinase inhibitors, evaluated in FaSSIF and FeSSIF.
In vivo oral pharmacokinetics in beagle dogs for hybrid nanoparticles containing nilotinib base, including reported comparison versus marketed nilotinib HCl.
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